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Biomedical subjects

L Molin

Publications and source records attributed to L Molin.

At least 37 records · Page 2Linked to original sources

Function of exudate neutrophils from skin in psoriasis.

Human neutrophils harvested from skin chambers containing autologous serum in psoriatic patients were compared with peripheral blood neutrophils by examining migration, phagocytosis, and oxidative activation. Random migration was reduced in exudate cells, whereas the chemotactic response to yeast-activated serum was evident not only in blood neutrophils, but also in exudate cells. The metabolic activation of exudate neutrophils, when stimulated with formyl-methionyl-leucyl-phenylalanine and measured as chemiluminescence, was enhanced by 50-400% compared to blood neutrophils. The chemiluminescence response to phorbol myristate acetate was on the other hand reduced to 35%. In the phagocytic assay, using C3bi- and IgG-opsonized yeast particles, exudate neutrophils from non-psoriatic healthy controls showed enhanced uptake of C3bi-coated yeast compared to blood neutrophils. In psoriatics, the blood neutrophils showed enhanced C3bi-mediated phagocytosis compared to non-psoriatic control cells. No further increase in C3bi-mediated phagocytosis was then seen in exudate cells from these patients. IgG-mediated phagocytosis was in contrast to C3bi similar between blood and exudate neutrophils in psoriatics and non-psoriatic controls. These experiments show that during exudation priming of different receptor-mediated processes can occur. However, no significant difference was observed between different functional capacities in exudate neutrophils from psoriasis patients and non-psoriatic controls.

Adult

Hydration of human stratum corneum studied in vivo by optothermal infrared spectrometry, electrical capacitance measurement, and evaporimetry.

Optothermal infrared spectrometry (OTIS) is a recently introduced method for specific measurement, in vivo, of water in the skin. In the present study the method proved well suited to register the increase in water content in stratum corneum following application of emollients. The results were compared with those obtained with a commercial instrument, the Corneometer, and the two methods were found to match very closely. Neither method indicated any difference in hydration of normal skin between young and elderly women. Evaporimetry was used to detect any influence on the water barrier function of the skin following application of emollients; even though the water content of the skin was significantly higher after emollient treatment, the transepidermal water loss remained unchanged.

Adolescent

Effects of single doses of UVA, UVB, and UVC on skin blood flow, water content, and barrier function measured by laser-Doppler flowmetry, optothermal infrared spectrometry, and evaporimetry.

The effect of single doses of ultraviolet (UV) radiation was studied in 6 healthy men of skin Type III. Test areas on the forearm were irradiated with 150 J/cm2 UVA, 0.5 MED, 1 MED, and 3 MED UVB, and 1 MED UVC. Test areas and control areas were followed up for 1 month by clinical assessment, laser-Doppler flowmetry, evaporimetry, and optothermal infrared spectrometry (OTIS). UVA produced immediate erythema; the reaction appeared later with the other wavelength regions. All responses peaked after 12-24 h. The degree of erythema of UV-induced inflammation assessed visually correlated closely with the increase in skin blood flow registered with the laser-Doppler flowmeter. No increase in transepidermal water loss, indicating damage to the epidermal barrier, could be recorded by evaporimetry except on the area irradiated with 3 MED of UVB, where 4 subjects showed a moderate increase after 2 weeks. Changes in water content in the uppermost part of the epidermis, mainly in the stratum corneum, were detected by OTIS. A decrease took place that was most pronounced in the area irradiated with 3 MED UVB. This decrease in the OTIS signal is probably due to a combination of increased thickness and decreased water content of stratum corneum. We believe that these 3 noninvasive methods, especially in combination, are useful in the evaluation of different aspects of UV reactions.

Adult

Thioguanine treatment in psoriasis.

The efficacy of thioguanine in the treatment of severe cases of psoriasis is demonstrated. This treatment is valuable in selected cases of severe psoriasis in whom other treatment is ineffective or impossible due to side effects. The effect of thioguanine on psoriasis lesions appears to run parallel with depression of the bone marrow. The bone marrow toxicity has to be considered. Patients previously treated with methotrexate are very sensitive to thioguanine and close follow up is mandatory with adjustment of the thioguanine dose according to blood white cell and thrombocyte levels.

Bone Marrow Diseases

Retinoids and systemic chemotherapy in cases of advanced mycosis fungoides. A report from the Scandinavian Mycosis Fungoides Group.

In cases of advance mycosis fungoides, the systemic chemotherapy combination of bleomycin, cyclophosphamide and prednisolone was given to 8 cases, and the same 3-drug combination with the addition of oral retinoids given to 12 cases. All cases were in a progressive phase of the disease. Remission was obtained in 5/8 cases treated with the combination and in 7/12 cases treated with the combination plus retinoids. The remissions were complete in half of the cases, but relapse occurred within 3 to 6 months in all but 2 cases. The two treatment patient groups were not fully comparable but the conclusion is that the addition of retinoids to systemic chemotherapy combination regimens is of some advantage. There still exists, however, need of more adequate treatment modalities in advanced mycosis fungoides.

Bleomycin

Oral retinoids in mycosis fungoides and Sézary syndrome: a comparison of isotretinoin and etretinate. A study from the Scandinavian Mycosis Fungoides Group.

Thirty-nine patients with mycosis fungoides in various stages or Sézary syndrome were treated with isotretinoin and 29 with etretinate as single drug therapy. Complete remission within 2 months was obtained with isotretinoin in 8 cases (21%) and partial remission in another 15 cases (38%). Etretinate induced complete remission in 5 cases (21%) and partial remission in 11 (46%). Only 1 case with Sézary syndrome went into partial remission. The first sign of remission occurred in 2 to 4 weeks. During continued treatment remissions could not always be maintained. Isotretinoin and etretinate were considered to be of equal potency in the treatment of mycosis fungoides.

Drug Eruptions

Neutrophil function in psoriasis: effects of retinoids.

The present investigation focused on the oxidative response of polymorphonuclear neutrophil leukocytes in psoriasis, in particular pustular psoriasis and how this response was affected by different retinoid compounds. In the active phase of pustular psoriasis, the neutrophil chemiluminescence response to the chemotactic peptide f-met-leu-phe and to phorbol myristate acetate was enhanced and correlated to the development of pustules, whereas cells from psoriasis vulgaris patients showed normal chemiluminescence response. Retinoids, particularly tretinoin (= retinoic acid) and isotretinoin caused a pronounced inhibition of the chemiluminescence response only in primed neutrophils in vivo and in vitro, whereas etretinate and the metabolite Ro 10-1670 was less inhibitory. Retinoic acid furthermore inhibited the Fc-mediated phagocytosis, but did not affect C3bi-mediated phagocytosis. These data suggest that the antiinflammatory effect of retinoids may operate by affecting neutrophil activation and function.

Acitretin

Comparative in vivo evaluation of a radioimmunoassay and a chromatographic assay for the measurement of digoxin in biological fluids.

The concentrations of digoxin in plasma and urine samples obtained from three healthy male volunteers, who received 1.2 mg of labeled digoxin perorally and intravenously, were simultaneously measured by a commercially available radioimmunoassay (RIA) and by a combined column thin-layer chromatographic assay (CA). The CA method, previously shown to assay digoxin specifically, was also used to monitor the individual digoxin metabolites. The results of this investigation showed that digoxin was significantly metabolized, particularly after peroral administration. The lower level of sensitivity of the RIA in plasma was 0.4 ng/mL. There were highly significant positive linear correlations between the values of the following parameters of digoxin as obtained by the RIA and CA methods: the concentrations in plasma and urine, the AUCs, and the cumulatively excreted amounts in urine. The two assays did not give completely identical results either with plasma or urine; the slopes of the regression lines deviated from unity in a significant number of cases. However, there was no relationship between the magnitude of the slopes of the regression lines and the extent of metabolism. It was concluded that the commercially available RIA evaluated was specific for digoxin and that the presence of digoxin metabolites did not affect the determinations.

Biotransformation

Long-term oral acyclovir treatment prevents recurrent genital herpes.

Thirty-three patients with frequently recurring genital herpes completed a randomized double-blind, crossover trial with oral acyclovir 200 mg 4 times a day and placebo for periods of 12 weeks. Five patients (15%) had full recurrence during acyclovir treatment and 31 (94%) while receiving placebo. The median time to first recurrence was 20 days for placebo and more than 84 days for acyclovir. It was concluded that acyclovir was well tolerated and an effective treatment to suppress the disease in selected cases of severe and frequently recurring genital herpes. However, the relapses seem to occur with the same rate as before, when the suppressive acyclovir treatment is stopped.

Acyclovir

Factors of importance for valid digitalis assays particularly for the determination of digoxin in plasma and urine.

Four commercial radioimmunoassay (RIA) kits for digoxin varied in precision (coefficient of variation, CV within-assays 5-14%) and accuracy (up to 40%). Thus it seems that such commercial RIA-kits can reach at best a CV within-assay of 5% and a similar variation between assays. Without a good control of the performance, the variation can increase 5-6 times. We found that the precision of digoxin RIA as performed at 27 Swedish laboratories using 10 different methods varied from 0.05 to 0.61 nmol/L in between-assay SD for a pool of 2.60 nmol/L. Up to 100% deviations between the highest and lowest reported concentration of a spiked plasma pool may occasionally occur. Such deviations mostly depend on the laboratory, but there are contributions from the kit and effects of the matrix as well. Matrix effects were observed in plasma samples from patients with uremia, acute myocardial infarction and treated with spironolactone to which digoxin was added to a concentration of 2.50 nmol/L. We found 10% underestimation by one method, 10% overestimation by two methods and 5% overestimation by a fourth method, respectively, with the above described samples. For a good judgement of a found plasma concentration value, calculation of a confidence interval is useful. This can be done by computer fitting of the standard curve after duplicate runs of standards and samples in random order. One source of error in RIA appears to be the use of inaccurate standards. We found that standards provided with different RIA-kits for digoxin varied up to 30%. Various physicochemical properties of cardiac glycosides, which could influence the assays were studied. Both digitoxin and digoxin are sparsely soluble in water (5.1 and 36 mumol/L, respectively). Methanol is a much better solvent, which dissolves 6.9 mmol/L of digoxin and 20-24 mmol/L of digitoxin. Chloroform is a good solvent for digitoxin (29-34 mmol/L) but not for digoxin (0.42 mmol/L). Partition of cardenolides between chloroform and water reflected their lipophilic or hydrophilic character. Thus, digitoxin had a high affinity to the organic phase (distribution constant KD = 10(3.65)), while the hydrophilic deslanoside was preferentially found in the aqueous phase (KD = 10(-3.08). Interestingly, the sugar moiety digitoxose in the digoxin molecule turned out to be a substituent that increased lipophilicity. Adsorption of cardiac glycosides occurs to plastics and glass from aqueous solutions. To overcome losses at low concentrations, the solutions must contain plasma, albumin, alcohol or similar solubility-increasing ingredients.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromatography, High Pressure Liquid

Some observations on various dose regimens of thymopentin treatment in rheumatoid arthritis.

Eight patients suffering from active rheumatoid arthritis were treated with thymopentin, 50 mg, administered as fractionated intravenous infusion over 10 min 3 times weekly for 3-20 weeks. Seven patients experienced clear-cut amelioration of symptoms and signs after just 2-4 weeks of treatment, and this improvement lasted for 6-8 weeks after thymopentin had been discontinued. Comparable positive results were observed in 2 patients who later continued thymopentin therapy by subcutaneous administration. Several subcutaneous dose regimens were tried; the optimal response appears to be achieved with 100-150 mg three times weekly and 150-200 mg twice a week, respectively. Because the subcutaneous therapeutic approach is more attractive to the patient-and also more practical for the physician-it should be investigated further.

Adjuvants, Immunologic

Thymopentin treatment of herpes simplex infections. An open, monitored, multicenter study.

Twenty-seven patients suffering from long-standing, severe, recurrent herpes simplex (14 labial and 13 genital) who had not responded adequately to prior therapy were recruited for this open, monitored study. They were treated with thymopentin 50 mg subcutaneously three times weekly for a period of 6 weeks. Clinical controls were performed once a week and then again 6 weeks after cessation of therapy; laboratory investigations were done at time points 0, 3, and 6 weeks. Additionally, information was collected with regard to the clinical course during the following year. Thirteen of 14 patients with labial infection and 10 of the 13 with genital herpes improved markedly (p less than 0.05) as shown by decrease in the relapse rate of at least 50%, shorter relapse episodes, and improvement of symptoms such as pain and itching. Fourteen of these 27 patients experienced no relapse for a period longer than 4 months after cessation of therapy. These favorable results were paralleled by a statistically significant increase in the T cell helper/suppressor ratio. This finding indicates that thymopentin acts as an immunodomulator; it is assumed that the activation of T helper cells induces-presumable via interleukin 2-the proliferation of cytotoxic T lymphocytes and natural killer cells which play a major role in the natural immune defense. No serious side effects of thymopentin were recorded.

Adjuvants, Immunologic

Thymopentin in chronic Trichophyton rubrum infection.

The case histories of 2 patients with chronic Trichophyton rubrum infections are presented. Both subjects had previously been treated systemically with griseofulvin, but had to be dropped from therapy due to adverse reactions. Topical treatment alone yielded unsatisfactory results. Thymopentin, 50 mg, administered subcutaneously three times weekly for a period of 6 weeks, induced rapid improvement within 3 weeks and almost complete remission 3 weeks later, although the fungi were still present on the skin. This beneficial effect lasted for up to 7 months after cessation of thymopentin therapy. Reinstitution of treatment produced the same response pattern. The clinical and immunological implications of these findings are briefly discussed; thymopentin is believed to enhance the suggested impaired cellular immunity in patients with chronic T. rubum infections.

Adjuvants, Immunologic